Introduction
Methods
Results
Study (trial registration no.)/study arm | Study duration, weeks | Blinding status | Background glucose-lowering therapya | Participants randomised, n | Female sex, n | Mean HbA1c, mmol/mol | Mean HbA1c, % | Mean body weight, kg | Mean diabetes duration, years | Mean age, years |
---|---|---|---|---|---|---|---|---|---|---|
SUSTAIN 1 [26] (NCT02054897) | 30 | Double-blind | None | |||||||
Semaglutide 0.5 mg | 128 | 68 | 64.9 | 8.1 | 89.8 | 4.8 | 54.6 | |||
Semaglutide 1.0 mg | 130 | 50 | 65.3 | 8.1 | 96.9 | 3.6 | 52.7 | |||
Placebo | 129 | 59 | 63.4 | 8.0 | 89.1 | 4.1 | 53.9 | |||
SUSTAIN 2 [27] (NCT01930188) | 56 | Double-blind | Metformin monotherapy (55%) or metformin+TZD (45%) | |||||||
Semaglutide 0.5 mg | 409 | 202 | 64.1 | 8.0 | 89.9 | 6.4 | 54.8 | |||
Semaglutide 1.0 mg | 409 | 204 | 64.4 | 8.0 | 89.2 | 6.7 | 56.0 | |||
SUSTAIN 3 [28] (NCT01885208) | 56 | Open-label | Monotherapy or dual combination with metformin (96.5%)/sulfonylurea (48.1%)/TZDs (2.3%) | |||||||
Semaglutide 1.0 mg | 404 | 185 | 67.9 | 8.4 | 96.2 | 9.0 | 56.4 | |||
GLP-1 RA (exenatide extended release) | 405 | 177 | 67.6 | 8.3 | 95.4 | 9.4 | 56.7 | |||
SUSTAIN 4 [29] (NCT02128932) | 30 | Open-label | Metformin monotherapy (48%) or metformin+sulfonylurea (52%) | |||||||
Semaglutide 0.5 mg | 362 | 165 | 65.4 | 8.1 | 93.7 | 7.8 | 56.5 | |||
Semaglutide 1.0 mg | 360 | 178 | 66.6 | 8.3 | 94.0 | 9.3 | 56.7 | |||
Basal insulin (glargine) | 360 | 165 | 65.4 | 8.1 | 92.6 | 8.6 | 56.2 | |||
SUSTAIN 5 [30] (NCT02305381) | 30 | Double-blind | Basal insulin monotherapy (16.7%) or basal insulin+metformin (83.3%) | |||||||
Semaglutide 0.5 mg | 132 | 58 | 67.9 | 8.4 | 92.7 | 12.9 | 59.1 | |||
Semaglutide 1 mg | 131 | 54 | 67.3 | 8.3 | 92.5 | 13.7 | 58.5 | |||
Placebo | 133 | 62 | 68.6 | 8.4 | 89.9 | 13.3 | 58.8 | |||
SUSTAIN 6 [31] (NCT01720446) | 104 | Double-blind | None, or monotherapy/dual-combination therapy with any glucose-lowering medication | |||||||
Semaglutide 0.5 mg | 826 | 331 | 71.6 | 8.7 | 91.8 | 14.3 | 64.6 | |||
Semaglutide 1.0 mg | 822 | 304 | 71.6 | 8.7 | 92.9 | 14.1 | 64.7 | |||
Placebo | 1649 | 660 | 71.6 | 8.7 | 91.9 | 13.6 | 64.6 | |||
SUSTAIN 7 [32] (NCT02648204) | 40 | Open-label | Metformin monotherapy | |||||||
Semaglutide 0.5 mg | 301 | 132 | 67.5 | 8.3 | 96.4 | 7.7 | 56.0 | |||
Semaglutide 1.0 mg | 300 | 139 | 66.2 | 8.2 | 95.5 | 7.3 | 55.0 | |||
GLP-1 RA (dulaglutide) | 598 | 267 | 65.9 | 8.2 | 94.5 | 7.3 | 56.0 | |||
SUSTAIN 9 [33] (NCT03086330) | 30 | Double-blind | SGLT2 inhibitor monotherapy (15.6%) or combination of SGLT2 inhibitor with metformin (71.5%)/sulfonylurea (12.9%) | |||||||
Semaglutide 1.0 mg | 151 | 62 | 64.1 | 8.0 | 89.6 | 9.8 | 57.5 | |||
Placebo | 151 | 64 | 64.5 | 8.1 | 93.8 | 9.6 | 56.6 | |||
SUSTAIN 10 [34] (NCT03191396) | 30 | Open-label | Metformin monotherapy or any combination of metformin (94.8%)/sulfonylurea (46.8%)/SGLT2 inhibitor (24.6%) | |||||||
Semaglutide 1.0 mg | 290 | 130 | 66.1b | 8.2 | 96.6 | 9.6 | 60.1 | |||
GLP-1 RA (liraglutide) | 287 | 120 | 67.2b | 8.3 | 97.2 | 8.9 | 58.9 | |||
SUSTAIN 11 [35] (NCT03689374) | 52 | Open-label | Metformin+insulin glargine | |||||||
Semaglutide 1.0 mg | 874 | 429 | 70.3 | 8.6 | 87.6 | 13.4 | 60.8 | |||
Prandial insulin (aspart) | 874 | 425 | 69.8 | 8.5 | 88.1 | 13.4 | 61.5 | |||
SUSTAIN CHINA [36] (NCT03061214) | 30 | Double-blind | Metformin | |||||||
Semaglutide 0.5 mg | 288 | 128 | 65.0b | 8.1 | 77.6 | 6.3 | 53.0 | |||
Semaglutide 1.0 mg | 290 | 136 | 65.0b | 8.1 | 76.1 | 6.7 | 53.0 | |||
SUSTAIN FORTE [37] (NCT03989232) | 40 | Double-blind | Metformin monotherapy (47%) or metformin+sulfonylurea (53%) | |||||||
Semaglutide 1.0 mg | 481 | 197 | 73.1 | 8.8 | 98.6 | 9.8 | 58.2 | |||
Semaglutide 2.0 mg | 480 | 201 | 73.4 | 8.9 | 100.1 | 9.2 | 57.9 | |||
Davies et al [38] (NCT01923181) | 26 | Open-label | None (17.1%) or metformin monotherapy (82.9%) | |||||||
Semaglutide 1.0 mg | 69 | 21 | 61.8b | 7.8 | 88.8 | 5.6 | 56.8 | |||
Placebo | 71 | 31 | 63.9b | 8.0 | 93.8 | 6.7 | 58.9 | |||
Iijima et al [39] (UMIN000040044) | 26 | Open-label | None (12.5%), metformin monotherapy (75%), or any combination of metformin/SGLT2 inhibitor/insulin glargine (12.5%)c | |||||||
Semaglutide 0.5 mg | 16 | 5 | 46.4 | 6.4 | 72.3 | 13.4 | 61.5 | |||
GLP-1 RA (dulaglutide) | 16 | 1 | 47.5 | 6.5 | 72.7 | 11.1 | 62.7 | |||
Seino et al [40] (NCT02254291) | 30 | Open-label | None | |||||||
Semaglutide 0.5 mg | 103 | 24 | 66.1b | 8.2 | 67.8 | 8.0 | 58.8 | |||
Semaglutide 1.0 mg | 102 | 27 | 63.9b | 8.0 | 70.8 | 7.8 | 58.1 | |||
Takahashi et al [41] (jRCTs1011200008) | 24 | Open-label | Monotherapy with any glucose-lowering medication or any combination of glucose-lowering medications (87.7% of participants received metformin either as monotherapy or combination therapy)d | |||||||
Semaglutide 0.5 mg | 50 | 18 | 63.0 | 7.9 | 79.8 | NR | 62.1 | |||
GLP-1 RA (liraglutide or dulaglutide) | 50 | 25 | 62.0 | 7.8 | 78.7 | NR | 60.9 | |||
SURPASS-1 [42] (NCT03954834) | 40 | Double-blind | None (54%) or previous oral medication use (46%) | |||||||
Tirzepatide 5 mg | 121 | 65 | 63.6 | 8.0 | 87.0 | 4.6 | 54.1 | |||
Tirzepatide 10 mg | 121 | 49 | 62.9 | 7.9 | 86.2 | 4.9 | 55.8 | |||
Tirzepatide 15 mg | 121 | 58 | 62.3 | 7.9 | 85.4 | 4.8 | 52.9 | |||
Placebo | 115 | 59 | 64.5 | 8.1 | 84.8 | 4.5 | 53.6 | |||
SURPASS-2 [6] (NCT03987919) | 40 | Open-label | Metformin monotherapy | |||||||
Tirzepatide 5 mg | 470 | 265 | 67.5 | 8.3 | 92.5 | 9.1 | 56.3 | |||
Tirzepatide 10 mg | 469 | 231 | 67.2 | 8.3 | 94.8 | 8.4 | 57.2 | |||
Tirzepatide 15 mg | 470 | 256 | 66.8 | 8.3 | 93.8 | 8.7 | 55.9 | |||
Semaglutide 1.0 mg | 469 | 244 | 66.7 | 8.3 | 93.7 | 8.3 | 56.9 | |||
SURPASS-3 [43] (NCT038882970) | 52 | Open-label | Metformin monotherapy (68%) or metformin+SGLT2 inhibitor (32%) | |||||||
Tirzepatide 5 mg | 358 | 158 | 65.8 | 8.2 | 95.4 | 8.5 | 57.2 | |||
Tirzepatide 10 mg | 360 | 165 | 66.0 | 8.2 | 94.3 | 8.4 | 57.4 | |||
Tirzepatide 15 mg | 358 | 165 | 66.3 | 8.2 | 94.9 | 8.5 | 57.5 | |||
Basal insulin (degludec) | 359 | 147 | 65.4 | 8.1 | 94.2 | 8.1 | 57.5 | |||
SURPASS-4 [44] (NCT03730662) | 52 | Open-label | Monotherapy with or any combination of metformin (95%)/sulfonylurea (54%)/SGLT2 inhibitor (25%) | |||||||
Tirzepatide 5 mg | 329 | 131 | 69.6 | 8.5 | 90.3 | 9.8 | 62.9 | |||
Tirzepatide 10 mg | 328 | 119 | 70.4 | 8.6 | 90.6 | 10.6 | 63.7 | |||
Tirzepatide 15 mg | 338 | 135 | 69.6 | 8.5 | 90.0 | 10.4 | 63.7 | |||
Basal insulin (glargine) | 1000 | 364 | 69.4 | 8.5 | 90.2 | 10.7 | 63.8 | |||
SURPASS-5 [45] (NCT04039503) | 40 | Double-blind | Insulin glargine monotherapy (17%) or in combination with metformin (83%) | |||||||
Tirzepatide 5 mg | 116 | 55 | 67.2 | 8.3 | 95.8 | 14.1 | 62.0 | |||
Tirzepatide 10 mg | 119 | 47 | 67.9 | 8.4 | 94.5 | 12.6 | 60.0 | |||
Tirzepatide 15 mg | 120 | 55 | 66.5 | 8.2 | 96.3 | 13.7 | 61.0 | |||
Placebo | 120 | 54 | 68.0 | 8.4 | 94.1 | 12.9 | 60.0 | |||
SURPASS-6 [46] (NCT04537923) | 52 | Open-label | Metformin+insulin glargine | |||||||
Tirzepatide 5 mg | 243 | 144 | 73.7 | 8.9 | 91.7 | 13.4 | 58.0 | |||
Tirzepatide 10 mg | 238 | 149 | 72.5 | 8.8 | 89.1 | 13.9 | 59.6 | |||
Tirzepatide 15 mg | 236 | 133 | 72.0 | 8.7 | 91.2 | 13.4 | 58.2 | |||
Prandial insulin (lispro) | 708 | 396 | 72.7 | 8.8 | 90.3 | 14.0 | 59.0 | |||
SURPASS-AP-COMBO [47] (NCT04093752) | 40 | Open-label | Metformin monotherapy (52.5%) or metformin+sulfonylurea (47.5%) | |||||||
Tirzepatide 5 mg | 230 | 96 | 72.4 | 8.8 | 77.7 | 7.4 | 53.1 | |||
Tirzepatide 10 mg | 228 | 102 | 71.7 | 8.7 | 76.3 | 7.9 | 53.5 | |||
Tirzepatide 15 mg | 229 | 100 | 71.4 | 8.7 | 76.2 | 7.6 | 54.3 | |||
Basal insulin (glargine) | 220 | 102 | 71.5 | 8.7 | 77.0 | 7.6 | 55.6 | |||
SURPASS J-COMBO [48] (NCT03861039) | 52 | Open-label | Monotherapy with sulfonylurea (30%), metformin (14%), α-glucosidase inhibitor (14%), TZD (14%), glinide (14%) or SGLT2 inhibitor (14%) | |||||||
Tirzepatide 5 mg | 148 | 29 | 69.7 | 8.5 | 77.7 | 8.5 | 57.7 | |||
Tirzepatide 10 mg | 147 | 34 | 70.2 | 8.6 | 76.6 | 9.1 | 56.9 | |||
Tirzepatide 15 mg | 148 | 44 | 70.0 | 8.6 | 78.3 | 8.5 | 56.5 | |||
SURPASS J-MONO [49] (NCT03861052) | 52 | Double-blind | None | |||||||
Tirzepatide 5 mg | 159 | 46 | 65.9 | 8.2 | 78.5 | 4.5 | 56.8 | |||
Tirzepatide 10 mg | 158 | 39 | 66.0 | 8.2 | 78.9 | 5.1 | 56.2 | |||
Tirzepatide 15 mg | 160 | 28 | 66.1 | 8.2 | 78.9 | 5.1 | 56.0 | |||
GLP-1 RA (dulaglutide) | 159 | 42 | 65.6 | 8.2 | 76.5 | 5.0 | 57.5 | |||
SURMOUNT-2 [50] (NCT04657003) | 72 | Double-blind | None or monotherapy with or any combination of metformin (89%), sulfonylurea (27%), SGLT2 inhibitor (20%), TZD (4%), or α-glucosidase inhibitor (1%) | |||||||
Tirzepatide 10 mg | 312 | 158 | 64.0 | 8.0 | 100.9 | 17.6 | 54.3 | |||
Tirzepatide 15 mg | 311 | 159 | 64.7 | 8.1 | 99.6 | 17.5 | 53.6 | |||
Placebo | 315 | 159 | 63.7 | 8.0 | 101.7 | 18.1 | 54.7 | |||
Frias et al [51] (NCT03131687) | 26 | Double-blind | None (9.8%) or metformin monotherapy (90.2%) | |||||||
Tirzepatide 5 mg | 55 | 21 | 66.1 | 8.2 | 92.8 | 8.9 | 57.9 | |||
Tirzepatide 10 mg | 51 | 21 | 66.1 | 8.2 | 92.7 | 7.9 | 56.5 | |||
Tirzepatide 15 mg | 53 | 31 | 65.0 | 8.2 | 89.1 | 8.5 | 56.0 | |||
Placebo | 51 | 22 | 63.9 | 8.0 | 91.5 | 8.6 | 56.6 | |||
GLP-1 RA (dulaglutide) | 54 | 30 | 65.0 | 8.1 | 89.8 | 9.3 | 58.7 | |||
Heise et al [7] (NCT03951753) | 28 | Double-blind | Metformin with or without one additional oral medication | |||||||
Tirzepatide 15 mg | 45 | 14 | 62.1 | 7.8 | 94.2 | 10.2 | 61.1 | |||
Semaglutide 1.0 mg | 44 | 10 | 60.7 | 7.7 | 92.7 | 12.7 | 63.7 | |||
Placebo | 28 | 7 | 62.9 | 7.9 | 98.8 | 11.0 | 60.4 |